Advances in clinical research of drug treatment based on renal fibrosis mechanism

doi:10.3877/cma.j.issn.2095-3216.2020.02.006

Abstract

Abstract:

Renal fibrosis is a common pathological feature of all advanced chronic kidney diseases, indicating that the renal injury has stepped into a common terminal pathway marked by remodeling of renal tissue structure and loss of renal function. At present, there is still a lack of effective therapeutic drugs for clinical treatment of renal fibrosis, and a large number of patients with renal fibrosis inevitably enter end-stage renal disease. Based on the progress of the molecular mechanism of renal fibrosis, a number of potential anti-fibrotic drugs have come into clinical trials in recent years. This review focused on some of the experimental drugs that have received intense attention, aiming to provide help for follow-up clinical researches.

Key words: Renal fibrosis, Therapeutic drug, Clinical trail

Congwei Luo, Xiaoyang He, Fenfen Peng, Yuxian Wang, Yihua Chen, Haibo Long. Advances in clinical research of drug treatment based on renal fibrosis mechanism[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2020, 09(02): 78-81.

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References 32

[1]	Humphreys BD. Mechanisms of renal fibrosis [J]. Annu Rev Physiol, 2018, 80: 309-326.
[2]	Nistor I, De Sutter J, Drechsler C, et al. Effect of renin－angiotensin－aldosterone system blockade in adults with diabetes mellitus and advanced chronic kidney disease not on dialysis: a systematic review and meta－analysis [J]. Nephrol Dial Transplant, 2017, 33(1): 12-22.
[3]	Liu BC, Tang TT, Lv LL, et al. Renal tubule injury: a driving force toward chronic kidney disease [J]. Kidney Int, 2018, 93(3): 568-579.
[4]	Tang PMK, Nikolic－Paterson DJ, Lan HY. Macrophages: versatile players in renal inflammation and fibrosis [J]. Nat Rev Nephrol, 2019, 15(3): 144-158.
[5]	Ikezumi Y, Suzuki T, Karasawa T, et al. Identification of alternatively activated macrophages in new－onset paediatric and adult immunoglobulin A nephropathy: potential role in mesangial matrix expansion [J]. Histopathology, 2011, 58(2): 198-210.
[6]	Eardley KS, Kubal C, Zehnder D, et al. The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease [J]. Kidney Int, 2008, 74(4): 495-504.
[7]	de Zeeuw D, Bekker P, Henkel E, et al. The effect of CCR2 inhibitor CCX140－B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial [J]. Lancet Diabetes Endocrinol, 2015, 3(9): 687-696.
[8]	Han H, Zhu J, Wang Y, et al. Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction [J]. J Pathol, 2017, 241(1): 80-90.
[9]	Dahan K, Debiec H, Plaisier E, et al. Rituximab for severe membranous nephropathy: a 6－month trial with extended follow－up [J]. J Am Soc Nephrol, 2017, 28(1): 348-358.
[10]	Lafayette RA, Canetta PA, Rovin BH, et al. A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction [J]. J Am Soc Nephrol, 2017, 28(4): 1306-1313.
[11]	Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study [J]. Arthritis Rheum, 2012, 64(4): 1215-1226.
[12]	Dekkers CCJ, Petrykiv S, Laverman GD, et al. Effects of the SGLT－2 inhibitor dapagliflozin on glomerular and tubular injury markers [J]. Diabetes Obes Metab, 2018, 20(8): 1988-1993.
[13]	Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy [J]. N Engl J Med, 2019, 380(24): 2295-2306.
[14]	Kohan DE, Barton M. Endothelin and endothelin antagonists in chronic kidney disease [J]. Kidney Int, 2014, 86(5): 896-904.
[15]	Wenzel RR, Littke T, Kuranoff S, et al. Avosentan reduces albumin excretion in diabetics with macroalbuminuria [J]. J Am Soc Nephrol, 2009, 20(3): 655-664.
[16]	Mann JF, Green D, Jamerson K, et al. Avosentan for overt diabetic nephropathy [J]. J Am Soc Nephrol, 2010, 21(3): 527-535.
[17]	Heerspink HJL, Parving HH, Andress DL, et al. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double－blind, randomised, placebo－controlled trial [J]. Lancet, 2019, 393(10184): 1937-1947.
[18]	Sharma K, Ix JH, Mathew AV, et al. Pirfenidone for diabetic nephropathy [J]. J Am Soc Nephrol, 2011, 22(6): 1144-1151.
[19]	Vincenti F, Fervenza FC, Campbell KN, et al. A phase 2, double－blind, placebo－controlled, randomized study of fresolimumab in patients with steroid－resistant primary focal segmental glomerulosclerosis [J]. Kidney Int Rep, 2017, 2(5): 800-810.
[20]	Voelker J, Berg PH, Sheetz M, et al. Anti－TGF－beta1 antibody therapy in patients with diabetic nephropathy [J]. J Am Soc Nephrol, 2017, 28(3): 953-962.
[21]	Ramazani Y, Knops N, Elmonem MA, et al. Connective tissue growth factor (CTGF) from basics to clinics [J]. Matrix Biol, 2018, 68－69: 44-66.
[22]	Adler SG, Schwartz S, Williams ME, et al. Phase 1 study of anti－CTGF monoclonal antibody in patients with diabetes and microalbuminuria [J]. Clin J Am Soc Nephrol, 2010, 5(8): 1420-1428.
[23]	Romagnani P, Remuzzi G, Glassock R, et al. Chronic kidney disease [J]. Nat Rev Dis Primers, 2017, 3: 17088.
[24]	Heerspink HJL, Persson F, Brenner BM, et al. Renal outcomes with aliskiren in patients with type 2 diabetes: a prespecified secondary analysis of the ALTITUDE randomised controlled trial [J]. Lancet Diabetes Endocrinol, 2016, 4(4): 309-317.
[25]	Chen YM, Chiang WC, Lin SL. Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update [J]. J Biomed Sci, 2017, 24(1): 84.
[26]	Perkins RM, Aboudara MC, Uy AL, et al. Effect of pentoxifylline on GFR decline in CKD: a pilot, double－blind, randomized, placebo－controlled trial [J]. Am J Kidney Dis, 2009, 53(4): 606-616.
[27]	Navarro－Gonzalez JF, Mora－Fernandez C, Muros de Fuentes M, et al. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial [J]. J Am Soc Nephrol, 2015, 26(1): 220-229.
[28]	Leporini C, Pisano A, Russo E, et al. Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: a systematic review and meta－analysis [J]. Pharmacol Res, 2016, 107: 315-332.
[29]	Tumlin JA, Galphin CM, Rovin BH. Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long－term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP－1 [J]. J Diabetes Res, 2013, 2013: 489869.
[30]	Davis TM, Ting R, Best JD, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study [J]. Diabetologia, 2011, 54(2): 280-290.
[31]	Brosius FC, Tuttle KR, Kretzler M. JAK inhibition in the treatment of diabetic kidney disease [J]. Diabetologia, 2016, 59(8): 1624-1627.
[32]	Levey AS, Gansevoort RT, Coresh J, et al. Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in collaboration with the US Food and Drug Administration and European Medicines Agency [J]. Am J Kidney Dis, 2019, 75(1): 84-104.

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